核苷（酸）类似物的补偿乙肝肝硬化患者无或小的食管静脉

StephenW

Research Article
The long-term benefits of nucleos(t)ide analogs in compensated HBV cirrhotic patients with no or small esophageal varices: A 12-year prospective cohort study

    Pietro Lampertico1, Federica Invernizzi1, Mauro Viganò2, Alessandro Loglio1, Giampaolo Mangia1, Floriana Facchetti1, Massimo Primignani1, Manol Jovani1, Massimo Iavarone1, Mirella Fraquelli3, Giovanni Casazza4, Roberto de Franchis5, Massimo Colombo1, ,

    1 “A.M. and A. Migliavacca” Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
    2 Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Italy
    3 Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
    4 Department of Biomedical and Clinical Sciences, Ospedale Luigi Sacco, Università degli Studi di Milano, Milan, Italy
    5 Division of Gastroenterology, Ospedale Luigi Sacco, Università degli Studi di Milano, Milan, Italy

    Received 22 October 2014, Revised 14 May 2015, Accepted 8 June 2015, Available online 19 June 2015



Background & Aims

Esophageal varices (EV) are a marker of disease severity in compensated cirrhosis due to hepatitis B virus (HBV) which predicts also the risk of hepatocellular carcinoma (HCC), clinical decompensation and anticipated liver related death. The dynamics and prognostic significance of EV in patients under long-term HBV suppression by nucleos(t)ide analogs (NUC), are poorly known.
Methods

A standardized protocol (Baveno) including 414 upper gastrointestinal (GI) endoscopies was applied to 107 HBeAg-negative compensated cirrhotic patients (93% Child-Pugh A) during a median of 12 (range 2 to 17) years of NUC therapy. Patients who initially started on lamivudine (LMV) and then developed resistance (LMV-R), were rescued by early administration of adefovir, or were switched to tenofovir. Surveillance included serum HBV DNA every three months and abdominal ultrasound every six months.
Results

Twenty-seven patients had baseline F1 EV which regressed in 18, remained unchanged in eight and progressed in one patient; the 12-year cumulative incidence of EV regression was 83% (95% CI: 52–92%). De novo F1/F2 EV developed in 6/80 patients with a 12-year cumulative incidence of 10% (95% CI: 5–20%). Six of seven patients with de novo varices or progression of pre-existing varices had either a clinical breakthrough due to LMV-R and/or developed a HCC. No bleedings from ruptured EV occurred, 12 patients died (9 HCC) and 15 were transplanted (13 HCC): the 12-year cumulative incidence of HCC and overall survival was 33% (95% CI: 24–42%) and 76% (95% CI: 67–83%), respectively.
Conclusions

Long-term pharmacological suppression of HBV in HBeAg-seronegative patients with compensated cirrhosis leads to a significant regression of pre-existing EV accompanied by a negligible risk of developing de novo EV.
Abbreviations

    EV, esophageal varices; NUC, nucleos(t)ide analogs; GI, gastrointestinal; LMV, lamivudine; LMV-R, lamivudine resistance; HCC, hepatocellular carcinoma; HBV, hepatitis B virus; HVPG, hepatic venous pressure gradient; EGDS, esophago-gastroduodenoscopy; PHG, portal hypertensive gastropathy; GOV, gastro-esophageal varices; IGV, isolated gastric varices; LT, liver transplantation; RWM, red wale marks; HIV, human immunodeficiency virus; US, abdominal ultrasound

Keywords

    Hepatitis B virus; Cirrhosis; Esophageal varices; Nucleos(t)ide analogs; Gastrointestinal bleeding; Hepatocellular carcinoma; HBsAg clearance; Transient elastography

    Corresponding author. Address: Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università di Milano, Via F. Sforza 35, 20122 Milan, Italy. Tel.: +39 0255035432; fax: +39 0250320700.

Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier Ireland Ltd. All rights reserved.

StephenW

研究论文
的核苷（酸）类似物的补偿乙肝肝硬化患者无或小的食管静脉曲张的长期效益：12年的前瞻性队列研究

    彼得Lampertico1，费德里卡Invernizzi1，毛罗Viganò2，亚历山德罗Loglio1，詹保罗Mangia1，弗洛里亚纳Facchetti1，马西莫Primignani1，Manol Jovani1，马西莫Iavarone1，米雷拉Fraquelli3，乔瓦尼Casazza4，罗伯托·德Franchis5，马西莫Colombo1，

    1“上午和A. Migliavacca“中心肝病，胃肠病学和肝病基金会IRCCS钙'格兰达Ospedale马焦雷位于Policlinico如Università德利阿布鲁Studi住宅米兰，米兰，意大利分部
    2科肝病的，Ospedale圣朱塞佩如Università德利阿布鲁Studi住宅米兰，意大利
    胃肠病学和内窥镜检查，基金会IRCCS钙'格兰达Ospedale马焦雷位于Policlinico如Università德利阿布鲁Studi住宅米兰，米兰，意大利的3部
    生物医学和临床科学，Ospedale路易吉·萨科如Università德利阿布鲁Studi住宅米兰，米兰，意大利4部
    5司消化，Ospedale路易吉·萨科如Università德利阿布鲁Studi住宅米兰，米兰，意大利

    收到22 2014年十月修订2015年5月14日接受8 2015年6月，可在线19 2015年6月



背景和目的

食管静脉曲张（EV）是在代偿性肝硬化疾病严重程度的标志物由于乙型肝炎病毒（HBV），这也预测肝细胞癌（HCC）的危险，临床失代偿和预期的肝相关死亡。动力和电动汽车的下长期抑制乙肝患者经核苷（酸）类似物（NUC）预后意义，鲜为人知。
方法

标准化协议（巴韦诺），包括414上消化道（GI）内镜应用于107 HBeAg阴性的补偿肝硬化患者（93％Child-Pugh分级A）为12（2〜17岁）NUC治疗的平均期间。患者最初开始拉米夫定（LMV），然后产生耐药性（LMV-R）是谁，被阿德福韦早期用药获救，或者被转换为替诺福韦。监测包括血清HBV DNA每三个月和腹部超声检查每半年一次。
结果

27例患者的基线F1 EV这倒退18，在八个保持不变，进步的一个病人; EV回归的12年累积发生率为83％（95％CI：52-92％）。从头F1 / F2电动汽车开发的6/80患者有10％（95％CI：5-20％），12年的累计发生率。六七例从头静脉曲张或预先存在的静脉曲张的发展有两种临床突破，由于LMV-R和/或开发出肝癌。从EV破裂出血没有发生，死亡12例（9 HCC）和15例移植（13 HCC）：HCC和总生存期的12年累积发生率为33％（95％CI：24-42％）和76％ （95％CI：67-83％），分别。
结论

乙肝病毒e抗原阴性的患者代偿性肝硬化长期药理抑制导致预先存在的EV伴随显影从头EV的风险可忽略一个显著消退。
缩写

    EV，食管静脉曲张; NUC，核苷（酸）类似物;胃肠道，胃肠道; LMV，拉米夫定; LMV-R，拉米夫定耐药;肝癌，肝细胞癌;乙肝病毒，B型肝炎病毒; HVPG，肝静脉压力梯度; EGDS，食管胃十二指肠镜检查; PHG，门脉高压性胃病; GOV，胃 - 食管静脉曲张; IGV，孤立性胃静脉曲张; LT，肝移植; RWM，红色征标记;艾滋病毒，人类免疫缺陷病毒;美国，腹部超声

关键词

    乙型肝炎病毒;肝硬化;食管静脉曲张;核苷（酸）类似物;胃肠道出血;肝癌; HBsAg清除;瞬时弹性成像

    通讯作者。地址：胃肠病学和肝病基金会IRCCS钙'格兰达Ospedale马焦雷位于Policlinico，UNIVERSITA米兰的Via F.斯福尔扎35，20122米​​兰，意大利的分部。电话：+39 0255035432;传真：+39 0250320700。

版权所有©2015年欧洲协会为肝脏的研究。发布时间由Elsevier爱尔兰有限公司保留所有权利。